Epidemiological evidence and laboratory experimentation over the past 20 yr supports the conclusion that immunity to group A streptococcal infection is type-specific. Antibodies directed against the M proteins, the antigens responsible for the specificity of the 50 or more serotypes of group A streptococci, are protective by virtue of their opsonic capacity. This subject has been thoroughly reviewed by Lancefield (1). Recent work has demonstrated that several small doses, e. g. 10/~g, of highly purified M proteins induce type-specific bactericidal antibodies in rabbits (2). The success of these latter experiments has been the impetus for this investigation on the development of a streptococcal vaccine for human use. With highly purified M proteins of types 12, 14, and 24, we have examined the degree of cutaneous hypersensitivity and the level of circulating antibodies in adults and infants. These studies have furnished data on the relative tolerance to M proteins and the possible extent of previous exposure to these serotypes. Secondary bactericidal antibody responses have been induced in adults injected with M protein vaccines without provoking untoward local or systemic reactions. I t is the purpose of this report to ex~mlne the feasibility of type-specific immunization of humans against group A streptococcal infections.
Materials and MethodsM Protcin.--Hi~hly purified M proteins were prepared from Group A streptococcal cell walls as previously described (3). A slight modification of the chromatographic procedure eliminated traces of nonspecifie antigens. To a column of carboxymethyl cellulose equilibrated with 0.03 u sodium acetate and containing the M protein sample was added 0.1 ~ sodium acetate buffer at pH 5.5. When the efeuent pH reached 5.5, a linear gradient of 0.1 M potassium phosphate buffer of inc~eAslng pH was applied to the column by adding equal volumes of buffers at pH 6.0, 6.5, and 7.0 to a Technicon "Autograd" mixing chamber for the final elution. Minor fractions of nonspedfic protein emerged prior and subsequent to the elution of the main peak of M protein near pH 6.